Polymerization of the microtubule-associated protein tau is responsible for the neurofibrillary pathology observed in Alzheimer's disease. This is a prevalent illness which causes dementia and death in the elderly. Attempts to understand the etiology of tau polymerization , and the subsequent impact of tau polymers on neuronal function have been limited by a paucity of suitable model systems. The goal of this research is to produce a cell culture system in which tau pathology can be selectively induced. Evidence indicates that tau polymers possess an ordered substructure which would necessarily result from the ordered structure of their constituent proteins. Amino acid sequences predicted to be involved in folding events associated with tau polymerization will be systematically altered by site directed mutagenesis, and he resultant proteins will be assayed for their ability to assemble. Tau sequences coding for proteins that demonstrate an increased potential for polymerization will be inserted into a.